The long term goals are to clarify the intrarenal mechanisms of blood flow and GFR regulation, and the interaction of these mechanisms with signals originating elsewhere in the body. Experiments will be conducted in 3 related areas. 1) The effect of acute hypertension on fluid and electrolyte transport in the proximal tubule and loop of Henle will be studied by in situ microperfusion to determine whether the loop of Henle responds to an increased fluid load delivered from the proximal tubule or directly to hypertension; to determine whether the proximal tubule response is triggered by intrarenal angiotensin II; and to determine whether the proximal tubule response involves modulation of Na-H exchange, NaCl transport, or both. A new method for measuring tubular flow rate will also be used to confirm that proximal tubule reabsorption is inhibited by hypertension. 2) Inter- and intracellular mechanisms involved in tubuloglomerular feedback (TGF) will be studied in Amphiuma means. The effect of changes in flow rate in the early distal tubule on transport of Cl across the epithelium will be measured, in combination with measurements of blood flow in afferent and efferent arterioles, to establish that there is a functional connection. Additional microelectrode measurements will be made in mesangial cells and in vascular smooth muscle cells of the afferent arteriole, to test hypotheses about the nature of the coupling. 3) Medullary blood flow rate will be measured in individual vasa recta to test the sensitivity to angiotensin II, to test an hypothesis about the interaction between angiotensin II and autoregulation, to determine whether prostaglandins modulate the action of angiotensin II on juxtamedullary efferent arterioles, and to test whether atrial natriuretic factor affects vasa recta flow independently on an effect on reabsorption from medullary collecting ducts.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK015968-16
Application #
3225492
Study Section
General Medicine B Study Section (GMB)
Project Start
1976-05-01
Project End
1991-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
16
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Southern California
Department
Type
Schools of Medicine
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90033
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Chon, Ki H; Raghavan, Ramakrishna; Chen, Yu-Ming et al. (2005) Interactions of TGF-dependent and myogenic oscillations in tubular pressure. Am J Physiol Renal Physiol 288:F298-307
Marsh, Donald J; Sosnovtseva, Olga V; Pavlov, Alexey N et al. (2005) Frequency encoding in renal blood flow regulation. Am J Physiol Regul Integr Comp Physiol 288:R1160-7
Walstead, Christopher; Yip, Kay-Pong (2004) Acute arterial hypertension inhibits proximal tubular fluid reabsorption in normotensive rat but not in SHR. Am J Physiol Regul Integr Comp Physiol 286:R726-33
Yip, Kay-Pong (2002) Coupling of vasopressin-induced intracellular Ca2+ mobilization and apical exocytosis in perfused rat kidney collecting duct. J Physiol 538:891-9
Chan, W L; Holstein-Rathlou, N H; Yip, K P (2001) Integrin mobilizes intracellular Ca(2+) in renal vascular smooth muscle cells. Am J Physiol Cell Physiol 280:C593-603
Yip, K P; Wagner, A J; Marsh, D J (2000) Detection of apical Na(+)/H(+) exchanger activity inhibition in proximal tubules induced by acute hypertension. Am J Physiol Regul Integr Comp Physiol 279:R1412-8
Chon, K H; Hoyer, D; Armoundas, A A et al. (1999) Robust nonlinear autoregressive moving average model parameter estimation using stochastic recurrent artificial neural networks. Ann Biomed Eng 27:538-47
Chon, K H; Chen, Y M; Holstein-Rathlou, N H et al. (1998) Nonlinear system analysis of renal autoregulation in normotensive and hypertensive rats. IEEE Trans Biomed Eng 45:342-53
Yip, K P; Tse, C M; McDonough, A A et al. (1998) Redistribution of Na+/H+ exchanger isoform NHE3 in proximal tubules induced by acute and chronic hypertension. Am J Physiol 275:F565-75

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